Dr. Bruce K. Tan is an Assistant Professor in the Department of Otolaryngology-Head and Neck Surgery at the Northwestern University Feinberg School of Medicine where his clinical practice is dedicated to rhinolology and olfactory loss. This career development award, under the mentorship of Drs. Robert P. Schleimer and Jay A. Gottfried, is focused on understanding the impact of B-cell mediated inflammation on the pathogenesis and olfactory loss associated with Chronic Sinusitis with Nasal Polyps (CRSwNP). CRSwNP is a prevalent inflammatory condition of the nose and paranasal sinuses that is a major cause of acquired olfactory loss. Currently, the inflammatory mechanisms driving this disease are poorly understood, thus limiting the classes of therapeutic agents utilized to treat this disease. We have increasing evidence and further preliminary data showing that B-cell inflammation and autoimmunity is present within some nasal polyps and may play an important role in the persistent inflammation associated with CRSwNP. The candidate is proposing two non-overlapping, but complementary, aims that seek to understand the role for B-cell mediated inflammation in olfactory loss in CRSwNP. In Aim 1, the candidate will utilize a set of superior turbinate tissue from CRSwNP patients and normal controls to evaluate the impact of B-cell inflammation in olfactory tissue. In Aim 2, he will establish if the autoantibodies found in CRSwNP are associated with molecular markers of pathogenicity and clinical evidence for persistent inflammation and olfactory loss following surgical therapy. During this award, Dr. Tan will also acquire practical training and coursework in immunology, biostatistics and study design. This training and the data generated though the proposed aims will form the basis for the candidate's future career as an independent investigator. PUBLIC HEALTH RELEVANCE: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a major cause of smell loss. The mechanisms driving inflammation in this disease are poorly understood and result in limited treatments in this disease. We have recently discovered that B-cell inflammation and autoimmunity are active in the noses of patients with CRSwNP and these studies aim to assess the impact of these forms of inflammation on smell loss.